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Single-cell RNA-seq analysis of human coronary arteries using an enhanced workflow reveals SMC transitions and candidate drug targets

Wei Feng Ma, Chani J. Hodonsky, Adam W. Turner, Doris Wong, Yipei Song, Nelson B. Barrientos, View ORCID ProfileClint L. Miller
doi: https://doi.org/10.1101/2020.10.27.357715
Wei Feng Ma
1Medical Scientist Training Program, University of Virginia, Charlottesville, VA 22908, USA
2Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
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Chani J. Hodonsky
2Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
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Adam W. Turner
2Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
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Doris Wong
2Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
3Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA
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Yipei Song
2Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
4Department of Computer Engineering, University of Virginia, Charlottesville, VA 22908, USA
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Nelson B. Barrientos
2Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
5Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA
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Clint L. Miller
2Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
3Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA
5Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22908, USA
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  • ORCID record for Clint L. Miller
  • For correspondence: clintm@virginia.edu
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Abstract

Recent advances in single-cell RNA sequencing (scRNA-seq) methods have enabled high-resolution profiling and quantification of cellular expression and transcriptional states. Here we incorporate automated cell labeling, pseudotemporal ordering, ligand-receptor evaluation, and drug-gene interaction analysis into an enhanced and reproducible scRNA-seq analysis workflow. We applied this analysis method to a recently published human coronary artery scRNA dataset and revealed distinct derivations of chondrocyte-like and fibroblast-like cells from smooth muscle cells (SMCs). We highlighted several key ligand-receptor interactions within the atherosclerotic environment through functional expression profiling and revealed several attractive avenues for future pharmacological repurposing. This publicly available workflow will also allow for more systematic and user-friendly analysis of scRNA datasets in other disease systems.

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations

    C7
    complement component C7
    CAD
    coronary artery disease
    CH
    chondrocytes
    CMP
    common myeloid progenitor cells
    DCN
    decorin
    DGIdb
    drug-gene interaction database
    EC
    endothelial cells
    EGFR
    epidermal growth factor receptor
    FB
    fibroblasts
    FBLN1
    fibulin 1
    GMP
    granulocyte-monocyte progenitor cells
    Mø
    macrophages
    MYH11
    myosin heavy chain 11
    SC
    stem cells
    sc/snATAC-seq
    single cell/single nucleus assay for transposase-accessible chromatin sequencing
    sc/snRNA-seq
    single cell/single nucleus RNA sequencin
    SMC
    smooth muscle cells
    UMAP
    uniform manifold approximation and projection
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    Posted October 27, 2020.
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    Single-cell RNA-seq analysis of human coronary arteries using an enhanced workflow reveals SMC transitions and candidate drug targets
    Wei Feng Ma, Chani J. Hodonsky, Adam W. Turner, Doris Wong, Yipei Song, Nelson B. Barrientos, Clint L. Miller
    bioRxiv 2020.10.27.357715; doi: https://doi.org/10.1101/2020.10.27.357715
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    Single-cell RNA-seq analysis of human coronary arteries using an enhanced workflow reveals SMC transitions and candidate drug targets
    Wei Feng Ma, Chani J. Hodonsky, Adam W. Turner, Doris Wong, Yipei Song, Nelson B. Barrientos, Clint L. Miller
    bioRxiv 2020.10.27.357715; doi: https://doi.org/10.1101/2020.10.27.357715

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